One of the major challenges in the use of multi-microelectrode arrays (MEA) in recording (in vitro and in vivo) neuronal network activities is the very low signal to noise ratio. This limits the monitoring to field potentials (˜100 μV) generated by action potentials and precludes the detection of sub-threshold synaptic potentials. Consequently, large efforts are devoted to the development of nanotechnologies to better couple excitable cells to electronic devices.
Currently, extracellular MEA is the only available technique for high temporal resolution for multi unit electrical recordings and stimulation. However, although this technique reflects synchronized sub threshold activity generated by ensembles of nearby neurons, it does not provide direct information on synaptic potential.
On the other hand, sharp intracellular microelectrodes and patch-electrodes enable to resolve sub-threshold events with an excellent signal to noise ratio. However, the use of such electrodes is limited to a relatively small number of neurons. In addition, the duration of recordings and stimulation is limited.
International application nos. WO2004/109282 [1] and WO2008/111047 [2] show that, in cultured non-vertebrate organism, Aplysia, by using an array of chemically functionalized electrodes, it is possible to obtain intracellular recordings of neuronal action potential and sub-threshold synaptic potentials. The biological processes enabling these recordings are in line with the observations that the electrodes were engulfed by the Aplysia's neurons and a high seal resistance was generated between the neuron and the electrode and finally that unexpected junctions were formed in the neuron-electrode interface supporting a bidirectional electrical coupling. Thus, an increased conductance of the membrane was observed.